DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Sun-Hyun | ko |
dc.contributor.author | Ryu, Shin-Young | ko |
dc.contributor.author | Yu, Weon-Jin | ko |
dc.contributor.author | Han, Young Eun | ko |
dc.contributor.author | Ji, Young-Sun | ko |
dc.contributor.author | Oh, Keunhee | ko |
dc.contributor.author | Sohn, Jong-Woo | ko |
dc.contributor.author | Lim, Ajin | ko |
dc.contributor.author | Jeon, Jae-Pyo | ko |
dc.contributor.author | Lee, Hyunsu | ko |
dc.contributor.author | Lee, Kyu-Hee | ko |
dc.contributor.author | Lee, Suk-Ho | ko |
dc.contributor.author | Berggren, Per-Olof | ko |
dc.contributor.author | Jeon, Ju-Hong | ko |
dc.contributor.author | Ho, Won-Kyung | ko |
dc.date.accessioned | 2015-11-20T12:36:25Z | - |
dc.date.available | 2015-11-20T12:36:25Z | - |
dc.date.created | 2014-03-27 | - |
dc.date.created | 2014-03-27 | - |
dc.date.created | 2014-03-27 | - |
dc.date.issued | 2013-07 | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.110, no.31, pp.12673 - 12678 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10203/201584 | - |
dc.description.abstract | Leptin is a pivotal regulator of energy and glucose homeostasis, and defects in leptin signaling result in obesity and diabetes. The ATP-sensitive potassium (K-ATP) channels couple glucose metabolism to insulin secretion in pancreatic beta-cells. In this study, we provide evidence that leptin modulates pancreatic beta-cell functions by promoting K-ATP channel translocation to the plasma membrane via AMP-activated protein kinase (AMPK) signaling. K-ATP channels were localized mostly to intracellular compartments of pancreatic beta-cells in the fed state and translocated to the plasma membrane in the fasted state. This process was defective in leptin-deficient ob/ob mice, but restored by leptin treatment. We discovered that the molecular mechanism of leptin-induced AMPK activation involves canonical transient receptor potential 4 and calcium/calmodulin-dependent protein kinase kinase beta. AMPK activation was dependent on both leptin and glucose concentrations, so at optimal concentrations of leptin, AMPK was activated sufficiently to induce K-ATP channel trafficking and hyperpolarization of pancreatic beta-cells in a physiological range of fasting glucose levels. There was a close correlation between phospho-AMPK levels and beta-cell membrane potentials, suggesting that AMPK-dependent K-ATP channel trafficking is a key mechanism for regulating beta-cell membrane potentials. Our results present a signaling pathway whereby leptin regulates glucose homeostasis by modulating beta-cell excitability. | - |
dc.language | English | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.subject | ACTIVATED PROTEIN-KINASE | - |
dc.subject | INSULIN-SECRETION | - |
dc.subject | METABOLISM | - |
dc.subject | RECEPTOR | - |
dc.subject | TRPC5 | - |
dc.subject | SENSITIVITY | - |
dc.subject | WEIGHT | - |
dc.subject | ENERGY | - |
dc.subject | MICE | - |
dc.subject | RAT | - |
dc.title | Leptin promotes K-ATP channel trafficking by AMPK signaling in pancreatic beta-cells | - |
dc.type | Article | - |
dc.identifier.wosid | 000322441500047 | - |
dc.identifier.scopusid | 2-s2.0-84881110501 | - |
dc.type.rims | ART | - |
dc.citation.volume | 110 | - |
dc.citation.issue | 31 | - |
dc.citation.beginningpage | 12673 | - |
dc.citation.endingpage | 12678 | - |
dc.citation.publicationname | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.identifier.doi | 10.1073/pnas.1216351110 | - |
dc.contributor.localauthor | Sohn, Jong-Woo | - |
dc.contributor.nonIdAuthor | Park, Sun-Hyun | - |
dc.contributor.nonIdAuthor | Ryu, Shin-Young | - |
dc.contributor.nonIdAuthor | Yu, Weon-Jin | - |
dc.contributor.nonIdAuthor | Han, Young Eun | - |
dc.contributor.nonIdAuthor | Ji, Young-Sun | - |
dc.contributor.nonIdAuthor | Oh, Keunhee | - |
dc.contributor.nonIdAuthor | Lim, Ajin | - |
dc.contributor.nonIdAuthor | Jeon, Jae-Pyo | - |
dc.contributor.nonIdAuthor | Lee, Hyunsu | - |
dc.contributor.nonIdAuthor | Lee, Kyu-Hee | - |
dc.contributor.nonIdAuthor | Lee, Suk-Ho | - |
dc.contributor.nonIdAuthor | Berggren, Per-Olof | - |
dc.contributor.nonIdAuthor | Jeon, Ju-Hong | - |
dc.contributor.nonIdAuthor | Ho, Won-Kyung | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | ACTIVATED PROTEIN-KINASE | - |
dc.subject.keywordPlus | INSULIN-SECRETION | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | TRPC5 | - |
dc.subject.keywordPlus | SENSITIVITY | - |
dc.subject.keywordPlus | WEIGHT | - |
dc.subject.keywordPlus | ENERGY | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | RAT | - |
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